T Jancel1, P A Shaw2, C W Hallahan3, T Kim4, A F Freeman5, S M Holland5, S R Penzak6. 1. Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, USA. 2. Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 3. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 4. Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA. 5. Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 6. Department of Pharmacotherapy, University of North Texas System College of Pharmacy, Fort Worth, TX, USA.
Abstract
WHAT IS KNOWN AND OBJECTIVE: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). METHODS: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. RESULTS AND DISCUSSION: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8-10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively. WHAT IS NEW AND CONCLUSIONS: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
WHAT IS KNOWN AND OBJECTIVE:Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). METHODS: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. RESULTS AND DISCUSSION: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8-10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively. WHAT IS NEW AND CONCLUSIONS:Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Entities:
Keywords:
paediatric; pharmacokinetics; posaconazole; therapeutic drug monitoring
Authors: Joanne G Wildenbeest; Matthijs W Oomen; Roger J Brüggemann; Martin de Boer; Yuma Bijleveld; J Merlijn van den Berg; Taco W Kuijpers; Dasja Pajkrt Journal: Pediatr Infect Dis J Date: 2010-06 Impact factor: 2.129
Authors: Marieke E B Welzen; Roger J M Brüggemann; J Merlijn Van Den Berg; Heleen W Voogt; Jos H Gilissen; Dasja Pajkrt; Nigel Klein; David M Burger; Adilia Warris Journal: Pediatr Infect Dis J Date: 2011-09 Impact factor: 2.129
Authors: Sonja Lüer; Steffen Berger; Miriam Diepold; Andrea Duppenthaler; Michael von Gunten; Konrad Mühlethaler; Rainer Wolf; Christoph Aebi Journal: Pediatr Blood Cancer Date: 2009-07 Impact factor: 3.167
Authors: Valeria A Bernardo; Shane J Cross; Kristine R Crews; Patricia M Flynn; James M Hoffman; Katherine M Knapp; Jennifer L Pauley; Alejandro R Molinelli; William L Greene Journal: Ann Pharmacother Date: 2013-06-04 Impact factor: 3.154
Authors: Ben De Pauw; Thomas J Walsh; J Peter Donnelly; David A Stevens; John E Edwards; Thierry Calandra; Peter G Pappas; Johan Maertens; Olivier Lortholary; Carol A Kauffman; David W Denning; Thomas F Patterson; Georg Maschmeyer; Jacques Bille; William E Dismukes; Raoul Herbrecht; William W Hope; Christopher C Kibbler; Bart Jan Kullberg; Kieren A Marr; Patricia Muñoz; Frank C Odds; John R Perfect; Angela Restrepo; Markus Ruhnke; Brahm H Segal; Jack D Sobel; Tania C Sorrell; Claudio Viscoli; John R Wingard; Theoklis Zaoutis; John E Bennett Journal: Clin Infect Dis Date: 2008-06-15 Impact factor: 9.079
Authors: Michael J Dolton; Roger J M Brüggemann; David M Burger; Andrew J McLachlan Journal: Antimicrob Agents Chemother Date: 2014-09-08 Impact factor: 5.191
Authors: Petr Sedlacek; Vladimir Vavra; Ivana Masova; Daniel Codl; Tana Laznickova; Ludmila Malaskova; Otakar Nyc; Jan Stary Journal: Mycoses Date: 2008-07-15 Impact factor: 4.377
Authors: Julio Maquera-Afaray; Medalit Luna-Vilchez; Blanca Salazar-Mesones; Diana Portillo-Alvarez; Luis Uribe-Ramirez; Graciela Taipe-Sedano; Carlos Santillán-Salas; José W López Journal: J Pediatr Pharmacol Ther Date: 2021-12-22
Authors: Lu Chen; Elke H J Krekels; Paul E Verweij; Jochem B Buil; Catherijne A J Knibbe; Roger J M Brüggemann Journal: Drugs Date: 2020-05 Impact factor: 9.546